This study was undertaken to gain further insight into the severely impaired natural killer (NK) activity we and others have previously observed in patients with chronic lymphocytic leukemia (CLL). Normal individuals' NK cells are large granular lymphocytes (LGL) that (A) bind to and lyse NK-sensitive cells, including K562, (B) express receptors for the Fc portion of IgG (FcR+ cells), and (C) express cell surface antigens reactive with monoclonal antibodies OKM1, 9.6, and OKT11A. We thus examined lymphocytes depleted of monocytes and B cells, from 6 CLL patients and 6 normal individuals, that were identified on the basis of binding to K562, expressing OKM1, or expressing receptors for the Fc portion of IgG. In the CLL patients studied, lymphocytes that bind to K562 cells, as well as OKM1+ cells isolated by fluorescence activated cell sorting, were morphologically similar to LGL of normal individuals, with the exception that more than 75% of the patientsx' cells were deficient in azurophilic cytoplasmic granules, which typify normal individuals LGL. Furthermore, although the percentages of the patients' FcR+ cells reactive with OKT11A, 9.6 and OKM1 were very similar to those of normals, the majority of the patients' FcR+ cells were deficient in azurophilic granules and lacked NK activity. These findings indicate that the impaired NK activity in CLL patients is associated with cells that are phenotypically and morphologically NK cells, but which lack azurophilic granules that are thought to play a role in NK-mediated lysis.

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